Maternal Near Miss According to World Health Organization Classification Among Women with a Hydatidiform Mole: Experience at the New England Trophoblastic Disease Center, 1994-2013.

OBJECTIVE: To investigate the frequency of potentially life-threatening conditions (PLTCs) and maternal near misses (MNMs) at the New England Trophoblastic Disease Center (NETDC) in recent years, when there has been earlier diagnosis of molar pregnancy. STUDY DESIGN: This study included patients with molar pregnancy at the NETDC between 1994 and 2013. Clinical and pathologic reports were reviewed. PLTC and MNM criteria and maternal deaths were searched in medical records using the World Health Organization criteria and classification. RESULTS: We identified 375 patients with molar pregnancy and no patient developed a MNM or maternal death. Only 6 (1.6%) had PLTCs (hemorrhage with hemodynamic instability, severe preeclampsia, respiratory distress, blood transfusion, and ICU admission). CONCLUSION: We observed a low rate of PLTC and no cases of MNMs or maternal deaths related to molar pregnancy, likely due to earlier diagnosis at the NETDC in recent years.

Management of Gestational Trophoblastic Diseases-An Update.

INTRODUCTION: Gestational trophoblastic disease is a spectrum of neoplastic abnormalities arising from fetal trophoblastic tissue. The range of the diseases in this group varies from relatively benign Hydatidifom mole (complete and partial mole) to highly malignant choriocarcinoma. METHODS: We have reviewed the available literature and discussed the management and follow up based on the current understanding of the natural history, extent and the prognosis of the disease. Key observations: Depending on the underlying pathology the disease can subside, progress or even metastasize and lead to death, if left untreated. The treatment of the disease is relatively simple and the disease is highly curable by single or multi agent chemotherapy. Appropriate and timely treatment not only saves the women from morbidity and death but also can help preserve their fertility. CONCLUSIONS: Management of Gestational disease should ideally be done in a specialized multi-disciplinary environment and the outcome of treatment in majority of the cases is very satisfactory.

Worldwide survey of the results of treating gestational trophoblastic disease.

OBJECTIVE: To determine factors influencing outcome for patients with gestational trophoblastic disease (GTD) from throughout the world. STUDY DESIGN: Physicians known to treat GTD were sent a questionnaire. RESULTS: There were 32 responses from 17 countries, totaling 26,153 patients. Of 14,093 patients with complete mole 20.6% developed trophoblastic neoplasia, and 5.7% died. There were 10,230 patients with partial mole, of whom 6.5% received therapy for neoplasia. There were 548 patients with post-term pregnancy choriocarcinoma, of whom 13.4% died. Of 137 patients with placental site trophoblastic tumor 16.1% died. The remaining 1,165 patients did not fit into a designated diagnostic category. The mortality rate for 2,818 patients with GTD primarily treated at a trophoblast center was 2.1%, as compared with 8% among 1,854 patients referred after failure of primary treatment (p < 0.01). CONCLUSION: Patients treated by physicians experienced in the management of trophoblastic disease have better results and survival.

Fatal cases of gestational trophoblastic neoplasia over four decades in the Netherlands: a retrospective cohort study.

OBJECTIVE: To describe fatal cases of gestational trophoblastic neoplasia (GTN) over four decades and evaluate whether treatment was given according to the protocol and reveal possible implications for future management. DESIGN: Retrospective cohort study. SETTING: The Netherlands. POPULATION: Women who died from GTN from 1971 to 2011. METHODS: Records from the Dutch Central Registry for Hydatidiform Moles and the Working Party on Trophoblastic Disease were used to identify fatal cases of GTN. MAIN OUTCOME MEASURES: Disease extent, risk classification, treatment regimens and cause of death. RESULTS: Twenty-six women died from GTN. In five cases GTN developed after a hydatidiform mole and in 19 cases following term pregnancy. Half of the women died between 1971 and 1980, when women were not yet classified as having low-risk or high-risk disease and were therefore not yet treated accordingly. A major decline in the number of deaths was seen after the first decade, with a further decrease from 1981 to 2011. Early death occurred in nine women. In four of these women, death was treatment-related. Women who died more than 4 weeks after the start of treatment mostly died from metastatic tumour (n = 14). CONCLUSIONS: The yearly number of women who died from GTN decreased considerably over the last four decades. Appropriate risk classification is essential to start optimal initial therapy and to prevent therapy resistance. Women with post-term choriocarcinoma represented a large proportion of the dead women and we propose that these women are considered as having high-risk disease.

Association between Breus' mole and partial hydatidiform mole: chance or can hydropic villi precipitate placental massive subchorionic thrombosis?

Breus' mole (massive subchorionic hematoma) is a rare entity most often found in the placentae of macerated stillborn fetuses. Previously considered to represent a postmortem event, recent evidence suggests that it occurs prior to fetal demise. A 23-week gestation male neonate was delivered of a 23-year-old gravida 3, para 2 woman and survived for 49 min. An autopsy with chromosomal studies resulted in a diagnosis of triploidy. Placental examination showed the presence of both Breus' mole and also partial hydatidiform mole. DNA samples extracted from portions of the fresh hematoma and from the fetal spleen were compared using molecular techniques. PCR analysis showed the presence of Y chromosome specific DNA in the placental clot, but a semiquantitative Southern blot demonstrated that roughly 85% of the clot DNA was of maternal origin. These findings suggest that Breus' mole represents primarily maternal thrombosis rather than fetal hemorrhage. We hypothesize that the partial mole could have contributed to the formation of the Breus' mole as some of the hydropic villi may have focally obstructed the maternal venous return from the intervillus space causing sluggish flow and promoting thrombosis. A review of the literature on Breus' mole shows that the majority of reported cases have not included cytogenetic findings. However, several authors have reported an association with triploidy and other chromosomal anomalies characterized by scattered placental hydropic villi. Thus, we suggest that obstruction of maternal venous return by hydropic villi may have played a contributory role in some of these other reported cases.

[Gestational trophoblastic tumors--a report of experiences]. / Gestationsbedingte Trophoblasttumoren--Ein Erfahrungsbericht.

The paper reports on clinical experiences of treatment of 58 patients with Gestational Trophoblastic Tumors (GTT), collected between 1978 and 1991. According to the Bagshawe-Score, 29 patients were at low-risk, 10 patients were assigned to the high-risk category. Among 29 metastatic cases, 5 patients had brain metastasis. In 33 patients, treatment started from the time of diagnosis. In 25 cases, treatment was initiated at other hospitals and patients were referred only after various unsatisfactory treatment measures. Low-risk patients were mainly subjected to methotrexate and folinic acid. Patients at medium-risk received a sequential chemotherapy. In high-risk patients we preferred the CHA-MOCA- or the EMA/CO-regimen. Treatment was successful in 91.4% of patients including all cases of low- and medium-risk. Five patients with brain metastases received systemic chemotherapy combined with intrathecal application of methotrexate and radiotherapy. Three of them could be cured. Patients taken from other hospitals more often underwent primary hysterectomies prior to systemic chemotherapy (40% versus 3%) and more often developed drug resistant tumors due to inadequate primary treatment. Five patients (8.6%) died from their disease, but only one of them received primary treatment in our department. Thus, the outcome (1/33 compared to 4/25) was significantly better for patients treated primarily at specialized centers.

Chemotherapy combined with surgery in the treatment of gestational trophoblastic disease (GTD).

Surgery combined with chemotherapy was applied in 34 out of 178 patients (19.1%) with GTD during treatment at the Institute of Oncology in Warsaw in the years 1977-1989. This mode of treatment was used twice as often in patients with MTD (Metastatic Tumour Disease) (31.6%) than in those with NMTD (Non Metastatic Tumour Disease) (14.2%). All 34 patients, who were operated on, had hysterectomy and 3 of them thoracotomy also. The most common indication for surgery was the chemoresistance of the disease, which had been stated in 53% of all treated surgically. All the patients with NMTD and those with good prognosis MTD, treated by combination of chemotherapy and surgery were cured, which confirms the efficacy of adjuvant surgery in these groups of patients. The role of surgery in patients with high-risk MTD is limited because of disseminated disease, frequently seen in this group.

[The DNA content in the cell nuclei of trophoblastic tumors]. / Soderzhanie DNK v iadrakh kletok opukholei trofoblasta.

The DNA content in cytotrophoblast (CTB) and syncytiotrophoblast (STB) cell nuclei was assayed in tissue sections of 7 hydatidiform moles (HM) and 27 choriocarcinomas (CH). The procedure involved Feulgen's reaction and scanning cytophotometry. The analysis of summarized histograms showed the DNA distribution in CTB cell nuclei, on the one hand, and that in STB, on the other, to differ significantly in both the tumors. The HM studied cases were referred to as two subtypes on the basis of such parameters as modal class value, its ploidy and degree of nuclear poly- and heteroploidy of CTB and STB. These characteristics were used to identify three patterns of CH. A pronounced modal class (2c--4c) was typical of type 1. A wider range of modal class (2c--10c or 4c--8c) was observed in type 2. Type 3 of tumor was characterized by a pronounced polyploidy with the absence of the modal class. The analysis of individual CTB and histograms showed no significant differences between HM and CH with respect to the DNA content. An increase in the share of highly polyploid cells was associated with a shorter survival of patients.

[New trends in trophoblastic disease].

In Japan, population-based trophoblastic disease registries were set up in the 1974s by the Registration Committee for Trophoblastic Disease (Japan Society of Obstet. & Gynecol.). The results indicate the following. 1. The incidence rates for trophoblastic disease show that the incidence of hydatidiform mole has been decreasing year by year from 10.2 to 5.9 throughout the observation period 1979-1986. But the incidence for hydatidiform mole per 1,000 pregnancies was from 1.83 to 1.91, and that per 1,000 deliveries was also from 2.84 to 2.93 throughout the observation period. The incidence of choriocarcinoma has also been decreasing year by year from 0.31 to 0.13 throughout the observation period. The frequency of choriocarcinoma after hydatidiform mole with complete remission was 0.32% (4/1, 171), but that after hydatidiform mole with no remission was 3.08% (4/130). The high risk groups for choriocarcinoma were hydatidiform mole over 40 years old, metastatic mole, and invasive mole. Five-year survival rate of choriocarcinoma with no metastatic foci was 100%, and that of metastatic choriocarcinoma was 59.2%. For cases treated with surgery combined with chemotherapy, 80.0 per cent of the cases survived 5 years compared with 71.4 per cent of the cases treated with chemotherapy alone and 67.7 per cent of the cases treated with surgery alone. The mortality for choriocarcinoma per 100,000 female population has been decreasing year by year from 0.123 to 0.065 throughout the observation period.

Pregnancy outcomes after successful chemotherapy for choriocarcinoma and invasive mole: long-term follow-up.

In order to preserve the fertility of young patients with choriocarcinoma and invasive mole, chemotherapy alone was given without hysterectomy in 265 cases from 1959 through 1980. By the end of 1985, 205 patients had become pregnant after recovery, with a total of 355 pregnancies. Among these, 23 were terminated by induced abortions, 26 as miscarriages, two as ectopic gestations, two as intrauterine deaths, and three as stillbirths. Among 303 livebirths (including four sets of twins), six infants died neonatally, three of whom were found to have congenital anomalies incompatible with life, and two died during infancy. All the remaining 295 children had normal growth and development, the oldest now being 25 years of age. The rates of fetal wastage, malformations, twin pregnancies, and neonatal and infantile deaths did not deviate from the normal. Cytogenetic study of the peripheral lymphocytes of 94 of the children revealed no increase of chromosomal aberrations. The rates of recurrence of disease and of death caused by recurrence of disease in these were not increased in comparison with those in patients who underwent hysterectomy. These data indicate that treatment of malignant trophoblastic neoplasms with chemotherapy alone is compatible with the preservation of fertility in most women.

Treatment of high-risk gestational trophoblastic disease with methotrexate, actinomycin D, and cyclophosphamide chemotherapy.

Seventy-three patients with metastatic high-risk gestational trophoblastic disease were treated with methotrexate, actinomycin D, and cyclophosphamide chemotherapy at the Brewer Trophoblastic Disease Center between 1968 and 1982. Forty-six patients were treated primarily with methotrexate, actinomycin D, and cyclophosphamide because of the presence of one or more high-risk factors. Twenty-seven additional patients who had not responded to initial single-agent chemotherapy with methotrexate and/or actinomycin D were subsequently treated with methotrexate, actinomycin D, and cyclophosphamide. Adjuvant surgery and radiotherapy were used in selected patients. The overall cure rate was 51% (37 of 73): 63% (29 of 46) for primary treatment and 30% (eight of 27) for secondary treatment (P less than .01). Several factors that influenced response to primary treatment with methotrexate, actinomycin D, and cyclophosphamide chemotherapy were determined: 1) clinicopathologic diagnosis of choriocarcinoma versus invasive mole (59 versus 100%), 2) metastases to sites other than the lung and/or vagina (44 versus 74%), 3) antecedent term gestation compared with hydatidiform mole or abortion (50 versus 75%), and 4) presence of three or more high-risk factors (27 versus 74%). There were no significant differences in cure rates during the course of the study period.

Registry and follow-up systems of trophoblastic disease in Japan.

With recent progress in chemotherapy, the prognosis of patients with trophoblastic disease has greatly improved, but the remission rate of patients with choriocarcinoma remains unfavorable. To improve the prognosis of these patients, early detection and early treatment are essential. Under the leadership of the Committee of Trophoblastic Disease of the Japan Society of Obstetrics and Gynecology, regional registries of trophoblastic disease were started in 1974. By 1982 14 prefectures with a total population of 46,893,620 were included in the registry. The early detection and treatment and follow-up made possible by the registry in addition to the introduction of advanced chemotherapy may be responsible for a rapidly decreasing trend in the death rate from this disease.

Maternal death associated with hydatidiform molar pregnancy.

Three maternal deaths with hydatidiform molar pregnancies associated with severe hemorrhage and coagulopathy are described. Symptoms of coagulation abnormalities are few in mild degrees of intravascular coagulation. This paper addresses the importance of anticipating a coagulopathy in hydatidiform molar pregnancy even before evacuation of the abnormal conceptus since evacuation aggravates fibrinolytic activity and therefore increases hemorrhage in these conditions.